The present invention relates to the use of valepotriatehydrins for the prevention and treatment of peptic ulcers and for the treatment of cramp-like disturbances in the gastrointestinal tract of mammals, including humans, and to novel valepotriate hydrins with peptic ulcer formation-inhibiting and motility-normalizing properties.
Valepotriates are compounds of Formula II ##STR1## wherein A denotes hydrogen, B denotes hydrogen or hydroxy, or A and B together denote a bond; and of the substituents R.sub.1, R.sub.2 and R.sub.3, one denotes an isovaleroyl group, another denotes an acetyl group, and the other denotes an acyl group of one of the following acids: isovalerianic acid, .beta.-methylvalerianic acid, .alpha.-isovaleroyloxyisovalerianic acid, .alpha.-acetoxyisovalerianic acid, .beta.-acetoxyisovalerianic acid, .beta.-acetoxy-.beta.-methylvalerianic acid, or .beta.-hydroxyisovalerianic acid. Valepotriates are known as the pharmacologically active ingredients of valerian and other plants of the family of the valerianeae See, for example, Thies, Tetrahedron 24: 313-317 (1968) and Thies et al, Planta Medica 41: 15-20 (1981). The known valepotriates include valtratum (A+B=a bond, R.sub.1 =acetyl, R.sub.2 =isovaleroyl, R.sub.3 =isovaleroyl), isovaltratum (A+B=a bond, R.sub.1 =isovaleroyl, R.sub.2 =isovaleroyl, R.sub.3 =acetyl), acevaltratum (A+B=bond, R.sub.1 =acetyl, R.sub.2 =isovaleroyl, R.sub.3 =acetoxyisovaleroyl), and didrovaltratum (A+B=a hydrogen atom each, R.sub.1 =isovaleroyl, R.sub.2 =isovaleroyl, R.sub.3 =acetyl). With the valepotriates, in valepotriate mixtures obtained from plants, analogous homocompounds are frequently present in which an isovaleroyl group of the corresponding valepotriate is replaced by .beta.-methylvaleroyl. Valepotriates are known for their effects on the central nervous system, especially calming and psychic stabilization, and also spasmolytic activity. These effects of valerian and its active ingredients have been used pharmaceutically for a long period of time.
In the course of work to elucidate the structure and to prepare chemical derivatives of valepotriates, certain halide and rhodano hydrins of the four valepotriates mentioned above have been prepared and described. Thus, for example, the iodohydrins, rhodanohydrins and bromohydrins of valtratum, acevaltratum and didrovaltratum (Tetrahedron 24: 313-317 and German Offenlegunsschrift Nos. 19 61 433 and 30 26 579), the chlorohydrin of valtratum (C.R. acad. Bulg. 28: 651 (1979)), and the iodohydrin and rhodanohydrin of isovaltratum (Tetrahedron 19: 3213-3226 (1973)) are known as intermediate products. The acetohydrin of didrovaltratum is also known as an intermediate product. Furthermore, certain hydrins of the best known valepotriates have been described wherein X signifies an acid group of an acid naturally occurring in valerian plants, particularly the isovaleroylhydrin of valtratum, acevaltratum, isovaltratum and didrovaltratum, together with the acetohydrins of valtratum and isovaltratum. See Tetrahedron Letters: 1171 (1976). No pharmacological properties have been disclosed heretofore for these valepotriate hydrins which have been prepared as intermediate products or which have otherwise been specifically described.
In German Offenlegunsschrift No. 31 12 732, a process for obtaining a valerian extract free of epoxy which possesses sedating-active ingredients, and which allegedly contains valepotriate hydrins, among others, is described. But no individual valepotriate hydrins or their effects are described more specifically.